Modulation of dexamethasone-induced thymocyte apoptosis by heat-shock protein 90-binding agents.

ABSTRACT

Heat-shock protein 90 (HSP90) is known to affect a variety of cellular activities. The present study showed that the HSP90-binding agents, geldanamycin, herbimycin A and radicicol, inhibited the murine thymocyte apoptosis induced by dexamethasone and was accompanied by the inhibition of the reduction of the mitochondrial transmembrane potential (delta psi m). HSP90-binding agents did not inhibit etoposide-induced apoptosis. The inhibition of dexamethasone-induced apoptosis was in part due to the interference of HSP90 with the glucocorticoid receptor, resulting in the inhibition of nuclear translocation of the receptor. The expression of inositol 1,4,5-triphosphate receptors, which were shown to be involved in dexamethasone-induced apoptosis, did not participate in the inhibition of apoptosis.